First in pregnancy continuous lactate monitoring using a minimally invasive microneedle device: A proof of concept study in healthy pregnant volunteers

Introduction: Labour physiology is poorly understood, and this lack of knowledge can result in interpretations which, in hindsight, lead to unnecessary interventions. Lactate levels are used to support decision making, especially around evolving sepsis during labour or post-partum haemorrhage management. Little is known about lactate levels as they relate to labour; they are presumed to rise during labour due to the anaerobic respiration brought about by physical exertion. A more dynamic measurement may be to continuously monitor lactate levels, which can more accurately show what and if something is wrong, but are more challenging to obtain as they are currently measured from single time point blood draws. Methods: A small, minimally-invasive, painlessly applied device that senses lactate levels in the interstitial fluid (ISF) continuously is described. The device has been tested on pregnant women who were asked to artificially raise their lactate levels through gentle exercise. The device uses a direct-electron transfer, modified lactate dehydrogenase enzyme that is immobilised onto a microneedle surface and provides a current response to lactate in proportion to its concentration. Blood draws were taken at regular intervals and lactate concentration was independently measured by mass-spectrometry. Results: Interstitial lactate mirrored trends in venous lactate in response to exercise. There was a time lag of around 5-10 minutes between the blood and ISF device current, consistent with the physiological lag from blood to ISF. Discussion: Increase in lactate was well predicted, but decrease once exercise had stopped was more complicated, which we attribute to kinetic effects as the lactate is cleared from the ISF. Application of the patch was observed to have a direct response on the amount of current measured, a firm thumb-pressure holding the patch onto the upper arm at the start of measurement was required for optimal functionality. Conclusion: This proof-of-concept study has shown the potential utility of a continuous lactate monitoring device for application during labour and childbirth. The device was shown to be functional and well-tolerated by pregnant women.